20 years after the first publication of the draft human genome: the journey ahead

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20 years of the human genome



Twenty years ago, Nature and Science published two pivotal papers revealing the nearly complete sequence of the human genome.

These studies were an unprecedent scientific breakthrough representing the output of 13 years of technologically innovative work that costed more than 3 billion dollars. It was just the beginning of a journey aimed at  better understanding the massive amount of information contained in our genome and its relevance to health and disease.

Since then, many things have changed and evolved. Human genome sequencing has now become faster, easier and cheaper, with a single genome being sequenced in days or hours at the cost of a few hundred euros. Genomic analyses launched a new era in biomedicine and clinical research, enabling in standard clinical practice the diagnosis of genetic disorders, the characterization of the genetic makeup of tumors and eventually helping the development of innovative personalized therapies.

Of course, the success of genomics has generated in a relatively short time a huge amount of sequence data, that have been shared among the scientific community and successfully used in preclinical and clinical research. For instance, rapid data sharing has been crucial in the current coronavirus crisis. The SARS-CoV-2 genome was identified very quickly and, once its sequence was released, the development of vaccines and effective diagnostic tests became possible.

Moreover, very relevant applications of genomics were developed, including pharmacogenomic tests that allow tailoring pharmacological treatments to each person's unique genetic makeup. Cancer genetic variations can affect drugs pharmacokinetics and pharmacodynamics; interestingly, genome wide analyses enable systematic studies of the inter-individual differences in anti-cancer drug response. That will help to improve the efficacy of individualized therapy by limiting drug toxicity while preserving antitumor activity. Moreover, germ line variants may predict tumor biology, thus helping to comprehend the genetic basis of cancer response to treatment. Of note, some genome‐wide association studies demonstrated that peculiar genes of the immune system were associated with the outcome and the efficacy of specific therapeutic interventions in cancer patients.

Genomic technologies can be also used for prenatal screening of genetic diseases, enabling early diagnosis and possible treatments, in utero or at birth. Even though prenatal whole genome sequencing is not yet clinically available, non-invasive prenatal testing based on the analysis of fetal DNA in the maternal serum, is now an option without any risk for miscarriage, provided by the genome-wide sequencing techniques.

In the past few years, the scientific community has shown an increasing interest toward the precision medicine field, giving rise to specific genomics research initiatives. In 2015, U.S. President Barack Obama promoted a research project, aimed to accelerate progress toward precision medicine, which has both short- and long-term goals: (i) to increase knowledge of the genetics and biology of cancer, in order to discover new and more effective tailored treatments; (ii) to bring precision medicine to the whole range of health and disease. To this end, the “All of Us Research Program” invites at least one million people across the U.S. to provide genetic data, biological samples and other information about their health.

Similarly, the U.K. Prime Minister David Cameron announced in 2012:The 100,000 Genomes Project”, aimed at sequencing 100,000 genomes from around 85,000 National Health Service patients, in order to improve diagnoses and treatments for individuals affected by rare inherited diseases and cancer.

Unquestionably, identifiable individual medical/genetic data posed privacy issue and underlined the necessity of a careful handling of this personal information: data safety should be paramount and the development of new identity protection strategies imperative, in order to safely manage the increasing amount of genomic data, successfully optimize data sharing and thus the advancement in public health research.

At this point, the question is: where is human genomics going in the next 20 years? The main expectations refer to the implementation of precision medicine, which uses genetic information to tailor interventions on the basis of the unique genetic profile of each individual to prevent and cure disease, from mental illness to cancer. Another ambitious task will be to understand how people’s genetic inheritance contributes to their response to infectious agents.

However, although all 3.2 billion base pairs have been sequenced and a huge amount of data generated, there is still a lack of understanding of the biological functions of every elements of human genome, a task that because of its complexity will require the implementation of artificial intelligence approaches.

Hopefully, in a couple of decades, the links between specific genomic data and distinctive phenotypes in health and disease will be elucidated, providing new insights into fundamental biology, new treatment options and translational opportunities, thus improving human health at large.